CaMKII is the most abundant kinase in neurons and is highly concentrated at synapses. The kinase has switch-like on/off properties that are activated during LTP induction. Mutations that interfere with this switching produce strong deficits in LTP and memory. Thus, understanding the detailed mechanisms by which CaMKII strengthens synapses will be important for understanding memory and its diseases. One of the most important questions in neuroscience is the molecular basis for memory storage at synapses. Although it is clear that CaMKII is critical for strengthening synapses, its role in maintaining this change (i.e. memory storage) requires further critical tests. An important recent observation is that LTP results in translocation of CaMKII to the synapse and an increase in the binding of CaMKII to the NMDAR. If this binding is abolished by mutation, then LTP induction is blocked. We therefore hypothesize that LTP is stored at the synapses by the CaMKII/NMDAR complex. A critical test of this hypothesis is to reduce the complex and determine whether this reverses LTP. A CaMKII inhibitor, CaMKIINtide interferes in vitro with the binding of CaMKII to the NMDAR. We will determine whether this and other agents that interfere with the CaMKII/NMDAR complex, when applied after LTP, can reverse LTP. Test will be performed to determine whether these inhibitors are actually reducing the CaMKII NMDAR complex in living cells. These tests will involve optical experiments that show the loss of GFP-CaMKII from the spine or biochemical experiment that test for a reduction in CaMKII-NMDAR coimmuoprecipitation. Positive results would strongly argue that the CaMKII-NMDA complex is critical for the storage of synaptic memory and would set the stage for studying the role of this complex in the maintenance of behavioral memory.